Design, synthesis and antibacterial activity of new phthalazinedione derivatives

Article abstract of DOI:10.2298/JSC091122028K

Dibenzobarallene (1) was utilized as the key intermediate for the synthesis of some new 2-substituted 1,4-dioxo-3,4,4a,5,10,10a-hexahydro-1H- -5,10-[1′,2′]-benzenobenzo[g]phthalazine: 2, 5a-d, 8a-c and 10. Condensation of 2 with benzaldehyde or anisaldehyde gave the corresponding acrylonitrile derivatives 3a and b, respectively. Thiophene derivatives 4a and b were obtained via the Gewald reaction of 2 with cyclohexanone or cyclopentanone, respectively. Treatment of 5d with acetyl chloride or p-toluenesulfonyl chloride afforded the corresponding esters 6 and 7, respectively. Cyclization of 8a-c with formalin afforded the corresponding triazine derivatives 9a-c. Ring opening of 10 with sodium hydroxide gave the corresponding triazole derivative 11, which when alkylated with pentyl bromide afforded the pentylthio derivative 12. Representative compounds of the synthesized products were established and evaluated as antibacterial agents.

Full text of DOI:10.2298/JSC091122028K

J. Serb. Chem. Soc. 76 (3) 329–339 (2011)
JSCS–4121
UDC 547.852.7+542.913:547.571:547.7:
615.281–188
Original scientific paper
Design, synthesis and antibacterial activity of new
phthalazinedione derivatives
*
ABD EL-GALIL M. KHALIL, MOGED A. BERGHOT and MOSTAFA A. GOUDA
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt
(Received 22 November 2009, revised 16 July 2010)
Abstract: Dibenzobarallene (1) was utilized as the key intermediate for the syn-
thesis of some new 2-substituted 1,4-dioxo-3,4,4a,5,10,10a-hexahydro-1H-
-5,10-[1’,2’]-benzenobenzo[g]phthalazine: 2, 5a–d, 8a–c and 10. Condensation
of 2 with benzaldehyde or anisaldehyde gave the corresponding acrylonitrile
derivatives 3a and b, respectively. Thiophene derivatives 4a and b were
obtained via the Gewald reaction of 2 with cyclohexanone or cyclopentanone,
respectively. Treatment of 5d with acetyl chloride or p-toluenesulfonyl chloride
afforded the corresponding esters 6 and 7, respectively. Cyclization of 8a–c with
formalin afforded the corresponding triazine derivatives 9a–c. Ring opening of
10 with sodium hydroxide gave the corresponding triazole derivative 11, which
when alkylated with pentyl bromide afforded the pentylthio derivative 12. Re-
presentative compounds of the synthesized products were established and eva-
luated as antibacterial agents.
Keywords: dibenzobarallene; phthalazine; thiophene; triazine; triazole; antibac-
terial agents.
INTRODUCTION
In the past decades, the synthesis of heterocyclic compounds was a subject
of great interest due to their wide applicability. Heterocyclic compounds occur
very widely in nature and are essential to life. Among a large variety of hetero-
cyclic compounds, heterocycles containing the phthalazine moiety are of interest
1–3
due to their pharmacological and biological activities (Fig. 1).
The phthalazine nucleus has pronounced pharmacological applications due
4
5
6
to its anticonvulsant, cardiotonic, and vasorelaxant, activities. In continuation
7,8
of efforts to identify new candidates that may be of value in designing new,
potent, selective and less toxic antimicrobial agent, herein the syntheses of some
new heterocycles incorporating the phthalazine moiety starting from dibenzoba-
9
rallene are reported.
*Corresponding author. E-mail: dr_mostafa_chem@yahoo.com
doi: 10.2298/JSC091122028K
329
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KHALIL, BERGHOT and GOUDA
(a)
(b)
Fig. 1. Antihypoxic, antipyretic agent (a),1 and HAV 3C inhibitor (b).2
RESULTS AND DISCUSSION
Analytical and spectral data of the synthesized compounds are given in the
Supplementary material.
Chemistry
The synthetic procedures adopted to obtain the target compounds are de-
1
picted in Schemes 1–3. Dibenzobarallene, and 3-(1,4-dioxo-3,4,4a,5,10,10a-he-
xahydro-1H-5,10-[1’,2’]-benzenobenzo[g]phthalazin-2-yl)-3-oxopropiononitrile
9,10
(2) were prepared according to previously reported methods.
Scheme 1. Gewald and Knoevenagel reactions of propiononitrile derivative 2.
Reaction of the propiononitrile derivative 2 with benzaldehyde or p-anis-
aldehyde, in the presence of sodium methoxide afforded the corresponding ac-
rylonitrile derivatives 3a and b, respectively. The structures of 3a and b were
1
supported by both their analytical and spectral data. The H-NMR spectrum of 3a
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SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF PHTHALAZINEDIONE DERIVATIVES
331
displayed a singlet signal at δ 7.8 ppm due to the methine proton of benzylidene.
In addition, compound 3b displayed two singlet signals at δ 3.8 and 7.7 ppm due
13
to OCH and methine protons, respectively. The C-NMR spectrum of 3a exhi-
3
bited signals at 118.3 and 112.4 ppm due to ethylenic carbons; in addition, 3b
exhibited, among others, signals at δ 114, 109 and 55.3 ppm due to ethylenic and
OCH carbons, respectively. Furthermore, the reaction of the propiononitrile
3
derivative 2 with cyclohexanone or cyclopentanone in a 1:2 molar ratio under
11–13
Gewald reaction condition
low yields (Scheme 1).
afforded the products 4a and b, respectively, in
Scheme 2. Reaction of dibenzobarallene (1) with some acid hydrazide derivatives.
Scheme 3. Synthesis of 1,2,4-triazine derivatives 9a–c.
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KHALIL, BERGHOT and GOUDA
1
13
The formulation of 4a and b were based on their mass, IR, H- and C-NMR
1
spectra. The H-NMR spectra of 4a and b displayed multiplet signals at δ 1.4–2.9
ppm and 1.4–3.0 ppm due to methylene and NH protons, respectively. The C-
13
-NMR spectrum of 4a displayed signals at δ 21.8, 22.1, 23.1, 23.8, 24.5, 24.9,
25.3, 25.7 and 26.9 ppm due to CH carbons; signals at δ 78.5 due to spiro-,
2
139.5, 128.2, 126.6 and 125.0 due to thiophene- and 194.8, 177.3 and 174.6 ppm,
due to carbonyl carbons. The mass spectrum of 4a exhibited the molecular ion
peak at m/z 549, which is in agreement with its molecular formula C H N O S,
33 31
3 3
in addition to other fragment ion peaks at m/z 506 and 493, 451, 371, 328, 275
and 259, which are illustrated in the fragmentation pattern shown in Fig. 2.
Fig. 2. Fragmentation pattern of compound 4a.
14
Additionally, reaction of adduct 1 with the appropriate acid hydrazide, in
acetic acid or DMF afforded the interesting phthalazinedione derivatives 5a–d;
15–18
an analogous reaction behavior has already been reported.
The structures of
5a–d were confirmed based on their spectral data. The IR spectra of 5a–d
–1
showed NH bands at 3374–3163 cm and three carbonyl bands at around 1729
–1
and 1660 cm . Moreover, the IR spectra of 5a and d showed additional bands at
–1
3387 and 1357 cm , due to –OH and –SO N groups, respectively. Furthermore,
2
1
the H-NMR spectrum of 5a displayed singlet signals at δ 10.8 and 11.4 ppm due
to OH and NH protons, respectively; also, 5d displayed a singlet signal at δ 10.8
13
ppm due to the NH proton of the phthalazine ring. The C-NMR spectrum of 5a
revealed signals at 173.9 and 177.4 ppm due to three carbonyl carbons. The mass
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333
spectrum of 5b gave the molecular ion peak at m/z 428 and 430 corresponding to
+
+
M and M +2, which are in agreement with its molecular formula C H ClN O .
25 17
2 3
In addition to the base, a peak at m/z 178 corresponding to anthracene was also
observed.
Treatment of 5d with acetic anhydride and p-toluenesulfonyl chloride in the
presence of a few drops of TEA yielded the phthalazine derivatives 6 and 7,
1
respectively. The H-NMR spectrum of 7 revealed a singlet signal at δ 2.4 ppm due
to the CH group; analogous behaviors were recorded in the literature (Scheme
3
15,17–20
2).
Furthermore, condensation of compound 1 with the appropriate 2-(arylamino)
21
acetic acid hydrazide in DMF yielded the corresponding phthalazinedione
derivatives 8a–c. The structures of 8a–c were based on spectral data. Thus, the
–1
–1
IR spectra of 8a–c showed 2NH bands at 3386–3365 cm and 3210–3197 cm
–1
–1
in addition to carbonyl bands at 1725–1717 cm and 1660–1658 cm . The mass
spectrum of 8b exhibited a molecular ion peak at m/z 437, which is in agreement
with its molecular formula C H N O , the base peak at m/z 178 corresponding
27 23
3 3
+
1
to anthracene and a fragment ion peak at m/z 259 due to M –anthracene. The H-
-NMR spectrum of 8b displayed singlet signals at δ 2.4, 4.8, 5.4 and 9.4 ppm due
to CH , NHAr, CH and NHCO protons, respectively.
3
2
Cyclization of the phthalazinediones 8a–c by reaction with 37 % formalde-
hyde in glacial acetic acid was studied with the aim of preparing the 1,2,4-tri-
22,23
azine derivatives 9a–c with potential biological activities (Scheme 3).
The
structures of 9a–c were based on analytical and spectral data. The IR spectra of
1
9a–c showed the absence of NH bands. The H-NMR spectrum of 9c revealed,
beside the disappearance of NH signal, the appearance of signals at δ 5.4 and 6.2
ppm due to CH CO and NCH N protons, respectively. The mass spectrum of 9c
2
2
+
exhibited a molecular ion peak at m/z 469 and 471 corresponding to M and
M +2, which is in agreement with its molecular formula C H ClN O . The
major fragment ion peaks at m/z 291 and 178 were attributed to M –anthracene
+
27 20
3 3
+
and anthracene, respectively (Scheme 3).
24–26
The remarkable biological importance of 1,2,4-triazole derivatives,
prompted an investigation of the synthesis of some new triazole derivatives of
expected antimicrobial activity. Thus, the adduct 1 was reacted with thiosemicar-
bazide in acetic acid or in THF to give 10. The structure of 10 was ascertained
+
through spectral data. Its mass spectrum exhibited the molecular ion peak M at
m/z 348, which is consistent with the molecular formula C H N O S, in ad-
19 15
3 2
+
dition to other fragment ion peaks at m/z 275 and 178 due to M –NCSNH and
2
anthracene, respectively. The derivative 10 was then heated with dilute aqueous
sodium hydroxide to yield the corresponding 5-thioxo-2,5-dihydro-1H-1,2,4-
-triazole derivative 11, the structure of which was confirmed by analytical and
spectral data (Scheme 4).
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KHALIL, BERGHOT and GOUDA
Scheme 4. Synthesis of triazole derivative 12.
The IR spectrum of 11 showed bands at 3136, 3111 (2NH), 2937–2866 (br,
–1
OH), 1709 (br, 3CO) and 1461, 1256 cm (C=S). Moreover, the mass spectrum
+
of 11 exhibited the molecular ion peak at m/z 203, corresponding to M –(CO ,
2
triazole moiety). Subsequent alkylation of 11 using n-pentyl bromide and a few
drops of TEA furnished the 5-(pentylthio)-2H-1,2,4-triazole derivative 12. The
spectral data of 12 are fully in accordance with the proposed structure, parti-
1
cularly the H-NMR spectrum that displayed signals at δ 0.8, 1.2–1.7, 3.6, 11.5
and 12.3 ppm due to CH , 3CH , CH S, NH and OH protons, respectively. The
3
2
2
mass spectrum of 12 added further support to the assigned structure. The mole-
cular ion peak appeared at m/z 420, the fragmentation pattern proceeded by two
different routes. In one pathway, the consecutive expulsion of CO and N from
2
2
+
M gave peaks at m/z 375 and 347, respectively. In the other route, the mole-
cular ion peak underwent fragmentation with the cleavage anthracene (m/z 178)
and another fragment ion at m/z 241. The synchronous loss of CO from the latter
2
species gave a fragment ion peak at m/z 197. The characteristic fragment ions are
shown in the fragmentation pattern given in Fig. 3.
Pharmacology
27
Twenty compounds were screened by the agar diffusion technique for their
in vitro antibacterial activities against two strains of bacteria Bacillus thurin-
giensis and Escherichia coli. The bacteria were maintained on nutrient agar.
DMSO showed no inhibition zones. The agar media were incubated with diffe-
rent cultures of the tested microorganism. After 24 h of incubation at 30 °C, the
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SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF PHTHALAZINEDIONE DERIVATIVES
335
diameter of inhibition zone (mm) was measured (Table I). Ampicillin and chlor-
amphenicol were purchased from the Egyptian market and used in a concen-
–1
tration of 2 mg ml as references.
Fig. 3. Fragmentation pattern of triazole derivative 12.
TABLE I. Inhibition zone (mean diameter of the disc in mm) as a criterion of the antibacterial
activities of the newly synthesized compounds
Compound
B. thuringiensis
E. coli
2
3a
3b
4a
4b
5a
5b
5c
5d
6
7
8a
8b
8c
9a
9b
22
27
28
21
18
17
32
16
27
26
40
18
16
20
17
18
17
15
16
24
18
23
16
20
19
20
17
15
25
17
22
21
22
16
18
17
16
16
16
14
13
22
19
20
9c
10
11
12
Ampicillin
Chloramphenicol
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KHALIL, BERGHOT and GOUDA
The results depicted in Table I revealed that compounds 3a, 3b, 4a, 5b, 5d,
6, 7 and 12 exhibited interestingly high antibacterial activities against the refe-
rence drugs.
Thus, it would appear that the introduction of arylidene, benzothiophene, sul-
fonyl, sulfonate or triazole moieties enhances the antibacterial properties of 3-
-(1,4-dioxo-3,4,4a,5,10,10a-hexahydro-1H-5,10-[1’,2’]-benzenobenzo[g]phthala-
zin-2-yl)-3-oxopropiononitrile (2) (Fig. 2). By comparing the results obtained for
the antibacterial activity of the compounds reported in this study with their struc-
tures, the following structure activity relationships (SARs) were postulated: i) com-
pounds 3a and 3b were more potent than compound 2, which may be attributed
to the introduction of the arylidene moiety; ii) compound 4a was more potent
than compound 2 due to presence of the benzothiophenetriazaepine moiety; iii) com-
pounds 5d, 6 and 7 were more potent than compound 2 due to the replacement of
the propiononitrile moiety by an arylsulfonyl moiety; iv) compound 7 was more
potent than 5d and 6, which may be due to the presence of two arylsulfonate
groups; v) compound 12 was more potent than compound 2 which may be at-
tributed to the replacement of the pyridazinedione moiety with a triazole moiety.
EXPERIMENTAL
All melting points are in degree centigrade and were measured on a Gallenkamp electric
melting point apparatus. Thin layer chromatography, TLC, analysis was performed on silica
gel 60 F254 pre-coated aluminum sheets. The IR spectra were recorded using the KBr wafer
technique on a Matson 5000 FTIR spectrometer, at the Faculty of Science, Mansoura Uni-
versity, India. The 1H-NMR spectra were determined on either a Varian XL 200 MHz instru-
ment at the Faculty of Science, Cairo University, Egypt, a Bruker WP 300 instrument at the
Georg-August University Göttingen, Germany, or a Brucker AC 300 instrument at the Eber-
hard-Karls University, Tubingen, Germany, in CDCl3 or DMSO solvent using TMS as the
internal standard. The 13C-NMR spectra were determined on a Brucker AC 300 instrument at
the Eberhard-Karls University, Tubingen, Germany, in CDCl3 or DMSO solvent using TMS
as the internal standard. The mass spectra were recorded on a Finnigan MAT 212 instrument
and the elemental analyses (C, H, and N) were performed in the Microanalytical Center of
Cairo University, Egypt.
2-[1,4-Dioxo-3,4,4a,5,10,10a-hexahydro-1H-5,10-[1’,2’]-benzenobenzo[g]-phthalazine-2-
-carbonyl]-3-(phenyl or p-methoxyphenyl)-acrylonitriles 3a,b
General procedure. A mixture of 2 (3.57 g; 0.01 mol) and benzaldehyde or p-anisalde-
hyde (0.011 mol) was added to a solution of sodium methoxide (0.34 g; 0.015 mol) in me-
thanol (20 ml). The reaction mixture was heated until a clear solution was obtained. The
reaction mixture was left overnight. The products were separated and crystallized from etha-
nol–benzene to give 3a and 3b, respectively.
Synthesis of (4H)-1,2,4-triazepin-7-one derivatives (4a,b)
General procedure. To a mixture of 2 (1.07 g; 0.003 mol), cyclohexanone or cyclo-
pentanone (0.006 mol) and sulfur (0.11 g; 0.0035 mol) in ethanol (30 ml) was added mor-
pholine (0.45 ml). The reaction mixture was heated on a water bath at 80–90 °C with stirring
for 1 h. Another portion of morpholine (0.15 ml) was added to the reaction mixture and stirred
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for another 3.5 h. The separated products were crystallized from ethanol–benzene to give 4a
and 4b as colorless crystals and a white powder, respectively.
Synthesis of 2-[(2-hydroxybenzoyl) or (4-chlorobenzoyl) or (pyridine-4-carbonyl) or (benzene-
sulfonyl)]-2,3,4a,5,10,10a-hexahydro-5,10[1’,2’]-benzenobenzo[g]phthalazine-1,4-dione (5a–d)
General procedure. A solution of 1 (2.76 g; 0.01 mol) and the corresponding acid hyd-
razide derivatives (0.01 mol) in DMF (20 ml) were refluxed for 3–4 h. The reaction mixture
was poured into a beaker containing ice and then the separated product was crystallized from
a suitable solvent to afford the phthalazine-1,4-diones 5a–d. 5a: white powder, 5b: crystal-
lization from DMF and separated as colorless needless crystals, 5c: crystallization from ben-
zene–ethanol and separated as colorless needless crystal, 5d: crystallization from DMF–me-
thanol.
Synthesis of acetic acid 3-(benzenesulfonyl)-4-oxo-3,4,4a,5,10,10a-hexahydro-5,10-[1’,2’]-
-benzenobenzo[g]phthalazin-1-yl ester (6)
A mixture of 5d (0.75 g; 0.0017 mol) and a few drops of TEA in (10 ml) acetic anhyd-
ride was warmed for 2 h. The separated product was crystallized from benzene–ethanol to
give 6.
Synthesis of toluene-4-sulfonic acid 3-(benzenesulfonyl)-4-oxo-3,4,4a,5,10,10a-hexahydro-
5,10-[1’,2’]-benzenobenzo[g]phthalazin-1-yl ester (7)
A mixture of 5d (1.3 g; 0.003 mol) p-toluenesulfonyl chloride (0.66 g; 0.0035 mol) and
few drops of TEA in dichloromethane (20 ml) was heated under reflux for 3 h. The solvent
was distilled off and the residue was washed with water and crystallized from methanol–ben-
zene to give 7.
Synthesis of 2-[1-oxo-2-[[(phenyl)/(p-tolyl)/(p-chlorophenyl)]-amino]-ethyl]-2,3,4a,5,10,10a-
hexahydro-5,10-[1’,2’]-benzenobenzo[g]-phthalazine-1,4-dione (8a–c)
General procedure. A solution of 1 (2.76 g; 0.01 mol) and the appropriate arylamino-
acetohydrazide, namely anilinoacetohydrazide, p-toluidinoacetohydrazide or p-chloroani-
linoacetohydrazide (0.01 mol) in DMF (20 ml) were heated under reflux for 3–4 h. The reac-
tion mixture was diluted with water. The separated products were filtered and crystallized
from a suitable solvent to give 8a–c. 8a: crystallized from methanol–benzene; white powder,
8b: crystallized from methanol–benzene; 8c: crystallized from benzene–ethanol.
Synthesis of {2-(phenyl)/ (p-tolyl)/(p-chlorophenyl)}-2,3,5a,6,11,11a-hexahydro-6,11-[1’,2’]-
-benzenobenzo[g]-1H-[1,2,4]triazino[1,2-b]phthalayine-4,5,12-trione (9a–c)
General procedure. A solution of 8a–c (0.0017 mol), formalin 37 % (0.3 ml, 0.0035
mol) and a few drops of glacial acetic acid in DMF (10 ml) were warmed on a water bath for
2–3 h. The reaction mixture was diluted with water. The separated product was filtered and
crystallized from a suitable solvent to give 9a–c. 9a: crystallized from benzene; 9b: crystal-
lized from benzene; colorless crystals; 9c: crystallized from benzene–ethanol; white powder.
Synthesis of N-[1,4-dioxo-3,4,4a,5,10,10a-hexahydro-1H-5,10-[1’,2’]-benzenobenzo[g]-
-phthalazin-2-yl]-thiourea (10)
A mixture of 1 (1.38 g; 0.005 mol) and thiosemicarbazide (0.53 g; 0.005 mol) in glacial
acetic acid (20 ml) was heated on a water path at 90 °C for 8 h. The separated product was
crystallized from benzene–ethanol to give 10. The above procedure was carried out in THF
(20 ml) instead of glacial acetic acid. The reaction mixture was heated under reflux for 2.5 h.
The separated product was crystallized to give 10.
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KHALIL, BERGHOT and GOUDA
Synthesis of 12-(5-thioxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)-9,10-dihydro-9,10-ethanoanthra-
cene-11-carboxylic acid (11)
A solution of 10 (0.6 g; 0.0017 mol) in 1 % sodium hydroxide (100 ml) was heated on
water bath at 95 °C for 2 h. The solution was left to cool and acidified with dilute hydro-
chloric acid. The separated product was crystallized from benzene–ethanol to give 11.
Synthesis of 12-[5-(pentylthio)-2H-1,2,4-triazol-3-yl]-9,10-dihydro-9,10-ethanoanthracene-
-11-carboxylic acid (12)
A solution of 11 (1.0 g; 0.0028 mol), 1-bromopentane (0.5 g; 0.0032 mol) and a few
drops of TEA in ethane (25 ml) was heated under reflux for 1 h. The reaction mixture was
diluted with water. The separated product was crystallized from ethanol–benzene to give 12.
In vitro antimicrobial activity
The tested compounds were evaluated by the agar diffusion technique,27 using a 2 mg ml-1
solution in DMSO. The test organisms were B. thuringiensis as gram-positive bacteria and E.
coli as gram-negative bacteria. A control using DMSO without the test compound was in-
cluded for each organism. Ampicillin and chloramphenicol in DMSO were used as the refe-
rence drugs.
CONCLUSION
In conclusion, we reported herein a simple and convenient route for the
synthesis of some new heterocycles based on the phthalazinedione moiety, which
were tested for their antibacterial activity.
SUPPLEMENTARY MATERIAL
Analytical and spectral data of the synthesized compounds are available electronically at
http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
Acknowledgements. Dr. S. Bondock and Dr. E. Abd El-Latif, Chemistry Department,
Faculty of Science, Mansoura University, for performing the spectral measurements, and Dr.
A. Mohamadin and Dr. A. El-Morsey, Botany Department, Faculty of Science, Mansoura
University, for the microbiological screening, are greatly acknowledged.
И З В О Д
СИНТЕЗА И АНТИБАКТЕРИЈСКА АКТИВНОСТ НОВИХ
ДЕРИВАТА ФТАЛАЗИНДИОНА
ABD EL-GALIL M. KHALIL, MOGED A. BERGHOT и MOSTAFA A. GOUDA
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt
Дибензобарелен (1) је коришћен као главни интермедијер у синтези нових 2-супсти-
туисаних (1,4-диоксо-3,4,4a,5,10,10a-хексахидро-1H-5,10-бензено-[1’,2’]-бензо[g]фталазина: 2,
5a–d, 8a–c и 10. Кондензацијом 2 са бензалдехидом или анизалдехидом добијени су нови
деривати акрилонитрила 3а и 3b. Деривати тиофена 4а и 4b добијени су Гевалдовом (Ge-
wald) реакцијом 2 са циклохексаноном или циклопентаноном. Реакцијом 5d са ацетил-хло-
ридом или para-толуенсулфонил-хлоридом добијени су одговарајући деривати триазина 6 и
7. Циклизацијом деривата 8а–c са формалдехидом добијени су одговарајући деривати три-
азина 9а–c. Отварањем прстена деривата 10 натријум-хидроксидом добијен је одговарајући
дериват 11 који алкиловањем са пентил-бромидом даје пентилтио дериват 12. Одабрана је-
дињења су испитана као антибактеријски агенси.
(Примљено 22. новембра 2009, ревидирано 16. јула 2010)
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